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Autoimmune Disease

Last updated 31 May 2026 · Immunology clinical guideline

📋 Key Information Summary

📋
  • Autoimmune diseases result from loss of immunological self-tolerance, with the immune system attacking host tissues via autoantibodies, immune complexes, or autoreactive T cells.
  • Australia has among the highest autoimmune disease prevalence globally, affecting approximately 5–8% of the population, with higher rates in Aboriginal and Torres Strait Islander communities.
  • Classification is divided into organ-specific (e.g., type 1 diabetes, Hashimoto thyroiditis, coeliac disease) and systemic (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis) categories.
  • Pathogenesis involves a combination of genetic susceptibility (HLA associations), environmental triggers (infections, UV, smoking), epigenetic dysregulation, and failure of immune checkpoint mechanisms.
  • Diagnostic workup centres on clinical assessment, targeted autoantibody panels (ANA, anti-dsDNA, anti-CCP, anti-TPO), inflammatory markers (ESR, CRP), and histopathological confirmation where indicated.
  • Anti-nuclear antibody (ANA) testing has high sensitivity but low specificity for SLE; a positive ANA alone is insufficient for diagnosis — correlate with clinical features and specific extractable nuclear antigen (ENA) profiles.
  • Management follows a stepwise approach: symptomatic relief (NSAIDs, analgesics) → corticosteroid bridging → conventional DMARDs (methotrexate, hydroxychloroquine, azathioprine) → biologic DMARDs (TNF-α inhibitors, rituximab) → targeted synthetic DMARDs (JAK inhibitors).
  • Hydroxychloroquine (Plaquenil®) is PBS-listed for SLE and rheumatoid arthritis; requires baseline and annual ophthalmological screening for retinal toxicity after cumulative doses exceeding 1000 g.
  • Methotrexate (Methoblastin®) remains the anchor DMARD for RA; mandatory monitoring includes FBC, LFTs, and renal function every 2–4 weeks initially, then every 2–3 months at stable dose.
  • Biologic DMARDs require screening for latent tuberculosis (IGRA or tuberculin skin test), hepatitis B/C serology, and varicella status before initiation.
  • Immunosuppressive therapy significantly increases susceptibility to infections — pneumococcal, influenza, and COVID-19 vaccination should be optimised prior to commencing biologics.
  • Aboriginal and Torres Strait Islander peoples experience higher disease burden, delayed diagnosis, and poorer outcomes — culturally safe care, community-based follow-up, and PBS co-payment concessions are essential.
  • Pre-conception counselling is critical for women of childbearing age, as methotrexate, mycophenolate, and cyclophosphamide are teratogenic; hydroxychloroquine and azathioprine are considered safe in pregnancy.

Introduction & Australian Epidemiology

Autoimmune disease encompasses a broad spectrum of disorders in which the adaptive or innate immune system mounts an inappropriate response against self-antigens, resulting in chronic inflammation and tissue destruction. This failure of immunological self-tolerance may manifest as organ-specific disease — where a single organ is targeted — or as systemic disease with multi-organ involvement.

Australia has one of the highest prevalences of autoimmune disease in the world. An estimated 1.2 million Australians (approximately 5–8% of the population) live with one or more autoimmune conditions. Rheumatoid arthritis alone affects approximately 456,000 Australians, while systemic lupus erythematosus (SLE) disproportionately affects women of childbearing age at a ratio of approximately 9:1 (female to male). Type 1 diabetes, coeliac disease, autoimmune thyroiditis, and inflammatory bowel disease collectively represent the most common organ-specific autoimmune conditions encountered in Australian primary care.

⚠️
Australian burden: Autoimmune diseases are among the leading causes of chronic disability in Australians aged 15–44 years. The total economic burden exceeds billion annually, encompassing healthcare costs, lost productivity, and informal care needs (AIHW, 2023).

Key epidemiological observations in Australia include:

  • Rheumatoid arthritis prevalence is 1.9% in women and 0.8% in men, with higher rates in Aboriginal and Torres Strait Islander populations.
  • SLE prevalence in Australia is approximately 45 per 100,000, with significantly higher rates in Indigenous Australians, particularly those of mixed ancestry.
  • Type 1 diabetes incidence in Australian children (0–14 years) is approximately 23 per 100,000 per year — among the highest rates globally.
  • Coeliac disease affects approximately 1 in 70 Australians, though many remain undiagnosed; active case-finding is recommended in at-risk groups.
  • Autoimmune thyroiditis (Hashimoto disease) is the most common autoimmune condition in Australia, with a prevalence of 3–5%.
  • Geographic and climatic variations influence disease patterns — UV radiation exposure is a recognised trigger for SLE flares in northern Australia, while vitamin D deficiency in southern latitudes may modulate immune function.

Sex and Gender Considerations

Approximately 78% of individuals affected by autoimmune disease are female. Oestrogen promotes B-cell survival and antibody production, while X-chromosome inactivation mosaicism may contribute to greater immune diversity and self-reactivity. These sex-based differences have significant implications for screening, diagnosis, and management in Australian clinical practice.

Autoimmune Disease clinical infographic — pathophysiology, clinical clues, diagnosis, imaging, and management
Tap or click image to enlarge — Autoimmune Disease: pathophysiology, clinical clues, diagnosis, imaging, and management.
Autoimmune Disease infographic, full size

Classification & Types

Autoimmune diseases are classified based on the target of immune attack and the breadth of organ involvement. This classification guides diagnostic workup, specialist referral pathways, and therapeutic strategies relevant to Australian practice.

Organ-Specific Autoimmune Diseases

In organ-specific autoimmune diseases, the immune response is directed against antigens confined to a single organ or tissue. These conditions are typically managed by organ-specific specialists in the Australian healthcare system.

Condition Target Organ Key Autoantibodies Typical Specialist Australian Prevalence
Hashimoto thyroiditis Thyroid Anti-TPO, anti-thyroglobulin Endocrinologist / GP 3–5%
Graves disease Thyroid TSH receptor antibodies (TRAb) Endocrinologist ~0.5%
Type 1 diabetes Pancreatic β cells Anti-GAD65, anti-IA-2, anti-ZnT8 Endocrinologist / Paediatrician ~0.5%
Coeliac disease Small bowel mucosa Anti-tTG IgA, anti-endomysial Gastroenterologist / GP ~1.4%
Autoimmune hepatitis Liver ANA, anti-SMA, anti-LKM-1 Gastroenterologist / Hepatologist ~24 per 100,000
Primary biliary cholangitis Intrahepatic bile ducts Anti-mitochondrial (AMA) Gastroenterologist / Hepatologist ~35 per 100,000
Multiple sclerosis CNS myelin Oligoclonal bands (CSF) Neurologist ~100 per 100,000
Myasthenia gravis Neuromuscular junction Anti-AChR, anti-MuSK Neurologist ~20 per 100,000
Autoimmune haemolytic anaemia Red blood cells Direct Coombs test positive Haematologist ~1–3 per 100,000/yr
Pemphigus vulgaris Skin / mucosal epithelium Anti-desmoglein 1 & 3 Dermatologist ~1–5 per 100,000

Systemic Autoimmune Diseases

Systemic autoimmune diseases involve immune-mediated damage to multiple organs and tissues, often through circulating autoantibodies, immune complex deposition, or widespread T-cell activation. These are predominantly managed by rheumatologists in collaboration with organ-specific specialists.

Condition Organs Affected Key Autoantibodies Hallmark Feature F:M Ratio
Systemic lupus erythematosus (SLE) Skin, joints, kidneys, brain, serosal surfaces ANA, anti-dsDNA, anti-Smith, anti-Ro/La Multi-system flares, nephritis 9:1
Rheumatoid arthritis (RA) Synovial joints (symmetric) RF, anti-CCP (ACPA) Symmetric polyarthritis, erosions 3:1
Systemic sclerosis (scleroderma) Skin, lungs, GI tract, vasculature Anti-Scl-70, anti-centromere, anti-RNA pol III Skin fibrosis, Raynaud, ILD / PAH 4:1
Sjögren syndrome Salivary, lacrimal glands, extraglandular Anti-Ro (SSA), anti-La (SSB), RF Sicca symptoms, fatigue 9:1
Systemic vasculitis (ANCA-associated) Small-to-medium vessels, kidneys, lungs c-ANCA (PR3), p-ANCA (MPO) GPA, MPA, EGPA subtypes 1:1
Dermatomyositis / Polymyositis Skeletal muscle, skin (dermatomyositis) Anti-Jo-1, anti-Mi-2, anti-MDA5 Proximal myopathy, heliotrope rash 2:1
Antiphospholipid syndrome Vascular endothelium (thrombotic) Anti-cardiolipin, anti-β2GP1, lupus anticoagulant Recurrent thrombosis, pregnancy loss 5:1

Mixed and Overlap Syndromes

A significant proportion of Australian patients present with features spanning multiple autoimmune categories. Overlap syndromes include:

  • Mixed connective tissue disease (MCTD): Features of SLE, systemic sclerosis, polymyositis, and RA with high-titre anti-U1 RNP antibodies.
  • Anti-synthetase syndrome: Myositis, interstitial lung disease, mechanic's hands, arthritis, Raynaud phenomenon, with anti-aminoacyl-tRNA synthetase antibodies.
  • Primary Sjögren syndrome with RA overlap: Common in clinical practice; requires integrated management of sicca symptoms and inflammatory arthritis.
  • Scleroderma-myositis overlap: Skin thickening with proximal muscle weakness; requires combined rheumatology and respiratory monitoring for interstitial lung disease.

Pathogenesis

The pathogenesis of autoimmune disease is multifactorial, involving an interplay between genetic predisposition, environmental triggers, immune dysregulation, and stochastic events. Understanding these mechanisms is essential for rational therapeutic targeting and risk stratification in Australian patients.

Failure of Central and Peripheral Tolerance

Immunological self-tolerance operates at two levels:

  • Central tolerance: In the thymus (T cells) and bone marrow (B cells), autoreactive lymphocytes are eliminated through negative selection. Defects in the AIRE (autoimmune regulator) gene impair thymic expression of peripheral tissue antigens, allowing autoreactive T cells to escape into the periphery. AIRE mutations cause autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED/APS-1).
  • Peripheral tolerance: Autoreactive lymphocytes that escape central deletion are controlled by regulatory T cells (Tregs, CD4+CD25+FoxP3+), anergy (functional unresponsiveness), and activation-induced cell death. Deficiency or dysfunction of Tregs is a hallmark of many autoimmune diseases.

Genetic Susceptibility

Genome-wide association studies (GWAS) have identified over 200 susceptibility loci for autoimmune disease. The HLA region on chromosome 6p21 remains the strongest genetic risk factor for most conditions:

Disease HLA Association Odds Ratio Non-HLA Genes
Rheumatoid arthritis HLA-DRB1 (shared epitope) 3–6 PTPN22, STAT4, CTLA4
SLE HLA-DR2, HLA-DR3 1.5–3 IRF5, STAT4, TNFAIP3, complement genes (C2, C4)
Type 1 diabetes HLA-DR3, HLA-DR4, HLA-DQ8 6–20 INS, PTPN22, IL2RA, CTLA4
Coeliac disease HLA-DQ2, HLA-DQ8 ~100 (necessary but not sufficient) SH2B3, IL18RAP, TAGAP
Ankylosing spondylitis HLA-B27 ~100 ERAP1, IL23R, IL12B
Multiple sclerosis HLA-DRB1*15:01 3 IL7R, IL2RA, CD58
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Australian context: HLA-B27 prevalence in the general Australian population is approximately 8–10%, but rises to 20–25% in Aboriginal and Torres Strait Islander populations, contributing to higher rates of spondyloarthropathy in these communities.

Environmental Triggers

Environmental factors are critical in initiating or exacerbating autoimmune disease in genetically susceptible individuals. Triggers with particular relevance in the Australian context include:

  • Ultraviolet radiation: Australia's high UV index (particularly northern latitudes) is a well-established trigger for SLE flares, inducing keratinocyte apoptosis and exposing intracellular autoantigens. UVB also modulates dendritic cell function and promotes type I interferon production.
  • Infections (molecular mimicry): Streptococcal pharyngitis triggers rheumatic heart disease; EBV is strongly associated with SLE and MS; Campylobacter jejuni triggers Guillain-Barré syndrome; hepatitis C is linked to cryoglobulinaemic vasculitis. Molecular mimicry occurs when microbial peptides share structural homology with self-antigens.
  • Smoking: Cigarette smoking is the strongest modifiable environmental risk factor for seropositive RA (anti-CCP positive), increasing risk 2–3-fold, particularly in HLA-DRB1 shared epitope carriers. Smoking also exacerbates SLE and Graves disease.
  • Silica and organic solvents: Occupational silica dust exposure (mining, construction) increases RA and SLE risk — relevant to Australia's resource sector. Organic solvents are associated with systemic sclerosis.
  • Vitamin D: Vitamin D deficiency, prevalent in southern Australian states during winter, modulates immune function and has been epidemiologically linked to increased MS and type 1 diabetes incidence. Optimal 25-hydroxyvitamin D levels ≥75 nmol/L are recommended.
  • Gut microbiome: Dysbiosis (reduced Firmicutes, increased Bacteroidetes) is implicated in RA, SLE, and IBD. Diet, antibiotic exposure, and geographic factors shape the microbiome in Australian populations.
  • Hormonal factors: Oestrogen upregulates B-cell activating factor (BAFF) and promotes class-switch recombination. Pregnancy modulates disease activity (RA improves in pregnancy but SLE may flare). Postpartum flares are common across many autoimmune conditions.

Immunopathological Mechanisms

Tissue damage in autoimmune disease is mediated through four classical mechanisms (Gell & Coombs classification):

Type II
Cytotoxic
Autoantibodies bind cell-surface antigens, triggering complement activation, ADCC, or direct functional interference.
Example: autoimmune haemolytic anaemia, Goodpasture syndrome, Graves disease (stimulatory)
Type III
Immune Complex
Circulating antigen-antibody complexes deposit in tissues (kidney, skin, joints), activating complement and recruiting neutrophils.
Example: SLE nephritis, serum sickness, ANCA-associated vasculitis
Type IV
Delayed-Type Hypersensitivity
Autoreactive CD4+ Th1/Th17 cells and CD8+ cytotoxic T cells directly damage tissue through cytokine release and cytotoxic granules.
Example: type 1 diabetes, rheumatoid arthritis, multiple sclerosis, Hashimoto thyroiditis

The Cytokine Network in Autoimmunity

Cytokine dysregulation is central to autoimmune pathogenesis and provides the molecular basis for biologic DMARD therapy. Key cytokine pathways targeted by current and emerging therapies include:

  • TNF-α: Pro-inflammatory cytokine central to RA, IBD, psoriasis, and spondyloarthropathy pathogenesis. Targeted by adalimumab (Humira®), etanercept (Enbrel®), infliximab (Remicade®).
  • IL-6: Drives acute-phase response, B-cell differentiation, and Th17 differentiation. Targeted by tocilizumab (Actemra®) and sarilumab (Kevzara®).
  • IL-17: Produced by Th17 cells; promotes neutrophil recruitment and tissue inflammation in psoriasis, spondyloarthropathy, and RA. Targeted by secukinumab (Cosentyx®) and ixekizumab (Taltz®).
  • IL-23: Drives Th17 cell maintenance and expansion. Targeted by guselkumab (Tremfya®) and risankizumab (Skyrizi®).
  • Type I interferons (IFN-α/β): Plasmacytoid dendritic cell overproduction of IFN-α is a hallmark of SLE. Targeted by anifrolumab (Saphnelo®), now TGA-approved in Australia for SLE.
  • BAFF (B-cell activating factor): Promotes B-cell survival and is elevated in SLE. Targeted by belimumab (Benlysta®).
  • JAK-STAT pathway: Intracellular signalling cascade downstream of multiple cytokine receptors. Targeted by tofacitinib (Xeljanz®), baricitinib (Olumiant®), upadacitinib (Rinvoq®).

Diagnostic Approach

The diagnostic approach to autoimmune disease requires integration of clinical assessment, serological testing, imaging, and histopathology. A systematic approach is essential to avoid diagnostic delay, which remains a significant issue in Australia — average time to diagnosis for conditions such as SLE and systemic sclerosis is 2–6 years from symptom onset.

Clinical Assessment

A thorough history and examination should focus on:

  • Symptom pattern: Duration, distribution (symmetric vs. asymmetric), chronicity, and systemic features (fatigue, weight loss, fevers, night sweats).
  • Organ-specific enquiry: Joint pain/swelling, skin rashes, Raynaud phenomenon, sicca symptoms, oral ulcers, alopecia, dysphagia, chest pain (serositis), visual changes, neurological symptoms.
  • Family history: Autoimmune diseases cluster in families; ~30% of patients with one autoimmune condition will develop another (polyautoimmunity).
  • Medication history: Drug-induced lupus (hydralazine, procainamide, isoniazid, minocycline) must be excluded.
  • Reproductive history: Recurrent miscarriage may indicate antiphospholipid syndrome.
  • Occupational and environmental exposures: Smoking, silica dust, solvents, UV exposure.

Laboratory Investigations

Tier 1 — Screening (GP-accessible, MBS-rebatable)

Available
Full blood count (FBC)
Cytopenias (anaemia of chronic disease, autoimmune haemolytic anaemia, thrombocytopenia, leucopenia) — MBS Item 65070.
Available
ESR and CRP
Non-specific inflammatory markers. ESR elevated in SLE, RA flares; CRP often normal in SLE unless serositis/infection. MBS Item 65070.
Available
Renal function and urinalysis
Creatinine, eGFR, urine ACR — screen for lupus nephritis, ANCA vasculitis renal involvement. MBS Item 66500.
Available
Liver function tests
Hepatocellular vs. cholestatic pattern — screen for autoimmune hepatitis, PBC. MBS Item 66515.
Available
ANA (anti-nuclear antibody) by IIF
Screening test for SLE, Sjögren, scleroderma, MCTD. Sensitivity ~95% for SLE but specificity ~50%. Titre ≥1:160 considered clinically significant. Note: Low-titre ANA (≤1:80) is present in ~15% of healthy Australians and does not indicate autoimmune disease. MBS Item 69300.
Available
Rheumatoid factor (RF) and anti-CCP
Anti-CCP has specificity >95% for RA and is more specific than RF. Double seropositivity (RF+ and anti-CCP+) predicts erosive disease. MBS Item 69306.

Tier 2 — Specialist-directed

Specialist
Extractable nuclear antigen (ENA) panel
Anti-dsDNA (SLE-specific, correlates with nephritis activity), anti-Smith (SLE-specific but low sensitivity), anti-Ro/La (Sjögren, neonatal lupus), anti-U1 RNP (MCTD), anti-Scl-70 (diffuse scleroderma). Recommended when ANA ≥1:160 with clinical suspicion.
Specialist
Complement levels (C3, C4, CH50)
Low C3 and C4 in active SLE (immune complex consumption); isolated C4 deficiency predisposes to SLE.
Specialist
ANCA (c-ANCA/PR3, p-ANCA/MPO)
ANCA-associated vasculitis screening — GPA (c-ANCA/PR3), MPA and EGPA (p-ANCA/MPO). Performed by ELISA after positive IIF screening.
Specialist
Antiphospholipid antibodies
Lupus anticoagulant, anti-cardiolipin IgG/IgM, anti-β2 glycoprotein I. Must be positive on two occasions ≥12 weeks apart for APS diagnosis. Essential in unexplained thrombosis or recurrent pregnancy loss.
Specialist
Cryoglobulins
Type I (haematological), Type II/III (mixed, associated with hepatitis C, SLE). Sample must be kept at 37°C until laboratory processing.
Specialist
Muscle-specific antibodies
Anti-AChR, anti-MuSK, anti-LRP4 — myasthenia gravis. Anti-Jo-1, anti-Mi-2, anti-MDA5 — inflammatory myopathies.

Histopathology

Tissue biopsy remains the gold standard for diagnosing and staging several autoimmune conditions:

  • Renal biopsy: ISN/RPS classification of lupus nephritis (Class I–VI) guides treatment intensity. Repeat biopsy warranted for suspected transformation or treatment failure.
  • Skin biopsy: Direct immunofluorescence (lupus band test), histopathology for vasculitis, pemphigus/pemphigoid subtyping.
  • Small bowel biopsy: Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (Marsh classification) in coeliac disease — though diagnosis may be made without biopsy in children with tTG IgA >10× ULN and positive EMA.
  • Salivary gland biopsy: Minor salivary gland biopsy (focus score ≥1) supports Sjögren syndrome diagnosis when serology is equivocal.
  • Liver biopsy: Interface hepatitis with plasma cell infiltrate in autoimmune hepatitis; staging guides treatment decisions.

Classification Criteria

Validated classification criteria assist in standardising diagnosis and facilitating clinical trial recruitment. Key criteria sets used in Australian practice include:

  • SLE: 2019 EULAR/ACR classification criteria (ANA ≥1:80 entry criterion, then additive weighted domains; ≥10 points = classified as SLE).
  • RA: 2010 ACR/EULAR classification criteria (joint involvement, serology, acute-phase reactants, symptom duration; ≥6/10 points = classified as RA).
  • Systemic sclerosis: 2013 ACR/EULAR criteria (skin thickening of fingers extending proximal to MCPs as sufficient criterion, or ≥9 points from 7 items).
  • ANCA-associated vasculitis: 2022 ACR/EULAR classification criteria for GPA, MPA, and EGPA.
  • Sjögren syndrome: 2016 ACR/EULAR criteria (anti-Ro positivity, focal lymphocytic sialadenitis, ocular staining score, Schirmer test, salivary flow; ≥4 points).
⚠️
Diagnostic pitfall: A positive ANA is not synonymous with autoimmune disease. Up to 15% of healthy Australians have a low-titre ANA. Do not order ANA as a general screen for fatigue or non-specific musculoskeletal symptoms — this leads to patient anxiety, unnecessary referrals, and healthcare costs. Order ANA only when clinical features suggest a specific connective tissue disease.

Referral Pathways in Australia

Clinical Scenario Referral Urgency
Inflammatory polyarthritis (suspected RA) Rheumatologist Within 6 weeks of symptom onset (treat-to-target)
Suspected SLE with renal involvement Rheumatologist + Nephrologist Urgent (days)
Suspected ANCA vasculitis Rheumatologist / Nephrologist Emergency (same day)
New-onset type 1 diabetes Endocrinologist / Paediatrician Urgent (1–2 days)
Suspected coeliac disease Gastroenterologist Routine (4–6 weeks)
New neurological deficit (MS suspected) Neurologist Urgent (1–2 weeks)

Management Principles

Management of autoimmune disease is guided by the principles of treat-to-target, stepwise immunosuppression, multidisciplinary care, and individualised risk-benefit assessment. The therapeutic armamentarium in Australia has expanded significantly with the PBS listing of biologic and targeted synthetic DMARDs.

General Therapeutic Principles

  • Treat to target: Aim for remission or low disease activity using validated composite measures (DAS28 for RA, SLEDAI-2K for SLE, CDAI/LDA). Reassess at 3–6 month intervals.
  • Step-up approach: Start with conventional synthetic DMARDs; escalate to biologic or targeted synthetic DMARDs if target not achieved.
  • Early intervention: Window-of-opportunity concept in RA — initiation of DMARD within 3 months of symptom onset improves long-term outcomes.
  • Combination therapy: Combining DMARDs (e.g., methotrexate + hydroxychloroquine + sulfasalazine) may be more effective than monotherapy in RA, with acceptable safety.
  • Bridging corticosteroids: Low-dose prednisolone (≤7.5 mg/day) or intramuscular methylprednisolone for acute flares; taper to minimum effective dose within 3–6 months.
  • Multidisciplinary care: Rheumatologist, GP, physiotherapist, occupational therapist, psychologist, podiatrist, and specialist nurse — coordinated through GP management plans (GPMP/TCA).

Pharmacological Therapy

Conventional Synthetic DMARDs

💊
Methotrexate
Methoblastin® · Antimetabolite (folate antagonist)
Adult dose Start 7.5–10 mg PO/SC once weekly; titrate to 15–25 mg/week. Co-prescribe folic acid 5 mg weekly (not on methotrexate day).
Paediatric dose JIA: 10–15 mg/m²/week PO/SC; max 25 mg/week.
Renal adjustment eGFR <30 mL/min: avoid. eGFR 30–59: reduce dose 50%.
Hepatic adjustment Avoid in significant hepatic impairment or active hepatitis B/C.
Monitoring FBC, LFTs, renal function — every 2 weeks × 6 weeks, then every 2–3 months.
PBS status ✔ PBS General Benefit
💊
Hydroxychloroquine
Plaquenil® · Generic · Antimalarial / immunomodulator
Adult dose 200–400 mg daily (≤5 mg/kg actual body weight).
Paediatric dose 3–5 mg/kg/day; max 400 mg/day.
Renal adjustment eGFR <30 mL/min: reduce dose.
Key adverse effects Retinal toxicity (cumulative risk after >1000 g total dose). Baseline ophthalmology exam + annual screening after 5 years (or sooner if risk factors).
PBS status ✔ PBS General Benefit
💊
Azathioprine
Imuran® · Purine antimetabolite
Adult dose Start 50 mg daily; titrate to 2–2.5 mg/kg/day based on response and TPMT status.
Key consideration Check TPMT/NUDT15 genotype before initiation. TPMT-deficient patients: avoid or drastically reduce dose.
Monitoring FBC every 1–2 weeks for first 8 weeks, then every 3 months. LFTs periodically.
PBS status ✔ PBS General Benefit
💊
Mycophenolate mofetil
CellCept® · Generic · Inosine monophosphate dehydrogenase inhibitor
Adult dose Start 500 mg BD; titrate to 1–1.5 g BD. Used for lupus nephritis, autoimmune hepatitis, vasculitis maintenance.
Key warning Teratogenic — Category X. Reliable contraception mandatory during and for 6 weeks after discontinuation.
PBS status ✔ PBS Restricted Benefit

Biologic DMARDs

⚠️
Pre-biologic screening checklist (mandatory):
  • Tuberculosis screening: IGRA (QuantiFERON-TB Gold or T-SPOT) or tuberculin skin test. Treat latent TB with 3 months isoniazid + rifapentine (3HP) or 6–9 months isoniazid before biologic initiation.
  • Hepatitis B serology (HBsAg, anti-HBc, anti-HBs). If HBsAg positive: antiviral prophylaxis (entecavir/tenofovir) before and during biologic therapy.
  • Hepatitis C serology. Active infection: treat to SVR before biologic initiation where possible.
  • Vaccination update: pneumococcal (Prevenar 13® + Pneumovax 23®), influenza, COVID-19, herpes zoster (Shingrix®). Live vaccines contraindicated on biologics.
  • Baseline bloods: FBC, LFTs, renal function, lipids (for JAK inhibitors).
💉
Adalimumab
Humira® · Biosimilars available (Hadlima®, Hyrimoz®, Idacio®) · Anti-TNF-α
Adult dose 40 mg SC every 2 weeks. Can increase to weekly in RA.
Indications (PBS) RA, AS, PsA, Crohn disease, ulcerative psoriasis, hidradenitis suppurativa, uveitis.
PBS status Authority Required
💉
Rituximab
MabThera® · Biosimilars available · Anti-CD20 (B-cell depletion)
Adult dose 1000 mg IV on days 1 and 15. Repeat cycle every 6 months based on disease activity.
Key indications RA (inadequate response to TNF inhibitor), ANCA vasculitis, refractory SLE.
PBS status Authority Required
💉
Belimumab
Benlysta® · Anti-BAFF/BLyS
Adult dose 10 mg/kg IV every 4 weeks (after loading at weeks 0, 2, 4) or 200 mg SC weekly.
Key indication Active SLE (SLEDAI ≥6) despite standard therapy; also approved for lupus nephritis.
PBS status Authority Required
💊
Tofacitinib
Xeljanz® · JAK1/JAK3 inhibitor
Adult dose 5 mg PO BD (RA, PsA, UC) or 11 mg SR daily.
Key safety Increased risk of VTE, MACE, and malignancy (particularly in patients >65 years and cardiovascular risk factors). Cardiovascular risk assessment mandatory before initiation.
PBS status Authority Required

Non-Pharmacological Management

  • Patient education and self-management: Structured programmes improve adherence and outcomes. Arthritis Australia provides educational resources.
  • Exercise: Regular moderate exercise (150 minutes/week) improves fatigue, cardiovascular fitness, and psychological well-being without worsening disease activity.
  • Diet: Mediterranean-style diet associated with reduced inflammatory markers in RA. Strict gluten-free diet is the only treatment for coeliac disease.
  • Smoking cessation: Absolute priority — smoking worsens RA, SLE, Graves disease, and MS. Offer NRT, varenicline, or bupropion as per RACGP guidelines.
  • Psychological support: Depression and anxiety prevalence is 2–3× higher in autoimmune disease. Cognitive behavioural therapy and acceptance and commitment therapy are recommended.
  • Vaccination: All patients should receive pneumococcal, influenza (annually), COVID-19, and herpes zoster vaccines. Live vaccines (MMR, varicella, yellow fever) should be administered ≥4 weeks before starting immunosuppression.
  • Cardiovascular risk management: Autoimmune disease is an independent cardiovascular risk factor. Aggressive management of hypertension, dyslipidaemia, and diabetes is essential. Use the modified CVD risk calculator incorporating disease activity.

Monitoring Framework

Parameter Frequency Purpose
Disease activity indices (DAS28, SLEDAI-2K, BASDAI) Every 1–3 months until target, then every 3–6 months Treat-to-target assessment
FBC Every 2–4 weeks initially, then every 2–3 months Drug toxicity (cytopenias)
LFTs Every 2–4 weeks initially, then every 2–3 months Methotrexate hepatotoxicity
Renal function + urinalysis Every 3–6 months Lupus nephritis, drug nephrotoxicity
Ophthalmology (hydroxychloroquine) Baseline + annual after 5 years (or earlier with risk factors) Retinal toxicity screening
Dual-energy X-ray absorptiometry (DEXA) Baseline if corticosteroid use ≥3 months; then every 1–2 years Glucocorticoid-induced osteoporosis
Lipid profile Before JAK inhibitor; then annually Cardiovascular risk (JAK inhibitor effect on lipids)
🚨
Safety-critical: Methotrexate is teratogenic (FDA Category X / Australian Category D). It must be discontinued at least 3 months before conception in both men and women. Adequate contraception is mandatory during treatment. Hydroxychloroquine and azathioprine are considered safe in pregnancy and should be continued to maintain remission.

Special Populations

🤰
Pregnancy
Safe to continue
Hydroxychloroquine, azathioprine (dose ≤2 mg/kg/day), tacrolimus, sulfasalazine (with folate), low-dose prednisolone.
Contraindicated — stop ≥3 months pre-conception
Methotrexate, mycophenolate mofetil, cyclophosphamide, leflunomide (requires cholestyramine washout), warfarin.
Specialist guidance required
Biologics — certolizumab pegol (Cimzia®) preferred as minimal placental transfer; other TNF inhibitors can be used until 2nd trimester. Rituximab: avoid if possible. JAK inhibitors: contraindicated.
Key considerations
Anti-Ro/La antibodies: risk of neonatal lupus (congenital heart block, neonatal rash) — foetal echocardiography from 16 weeks. Antiphospholipid syndrome: low-dose aspirin + LMWH throughout pregnancy.
👶
Paediatrics
Juvenile idiopathic arthritis (JIA)
Most common paediatric rheumatic disease in Australia (~1 per 1000 children). Methotrexate is first-line systemic DMARD. Biologics: etanercept and adalimumab are PBS-listed for polyarticular JIA ≥4 years.
Paediatric SLE
More aggressive than adult-onset; higher rates of nephritis and neuropsychiatric involvement. Hydroxychloroquine + mycophenolate or cyclophosphamide for nephritis.
Type 1 diabetes
Rising incidence in Australian children. Teplizumab (Tzield®) — anti-CD3 — now TGA-approved for stage 2 T1D (autoantibodies + dysglycaemia) to delay onset. Continuous glucose monitoring (CGM) funded through NDSS for all Australians with T1D.
👴
Elderly (≥65 years)
Late-onset RA
Often seronegative; differential includes polymyalgia rheumatica (PMR). Lower methotrexate starting dose (5–7.5 mg/week). Biologics: higher infection risk; screen more aggressively for TB and malignancy.
Corticosteroid caution
Accelerated osteoporosis, diabetes, cataracts, myopathy. If on prednisolone ≥3 months: bisphosphonate prophylaxis (alendronate 70 mg weekly, PBS General Benefit).
JAK inhibitors
Increased VTE and MACE risk in patients ≥65 years — avoid tofacitinib as first-line in this age group.
🫘
Renal Impairment
Methotrexate
eGFR <30 mL/min: contraindicated. eGFR 30–59: reduce dose 50%. Monitor more frequently.
Cyclophosphamide
Dose reduction required in renal impairment (GFR-based dosing per Euro-Lupus or NIH protocols). Mesna co-administration to prevent haemorrhagic cystitis.
NSAIDs
Avoid in eGFR <30 mL/min. Contribute to AKI, hyperkalaemia, and interstitial nephritis.
Rituximab
No dose adjustment; safe in dialysis patients. Monitor for delayed neutropenia.
🫁
Hepatic Impairment
Methotrexate
Avoid in active hepatitis B/C, significant hepatic fibrosis, or heavy alcohol use. Serial FibroScan if prolonged use.
Leflunomide
Hepatotoxic — contraindicated in significant liver disease. Monitor LFTs monthly for first 6 months.
Biologics
Generally safe in liver disease. Screen for hepatitis B reactivation risk; antiviral prophylaxis if HBsAg positive.
🦠
Immunocompromised
Infection risk
Combination immunosuppression (e.g., methotrexate + biologic + corticosteroids) triples serious infection risk. Aim to minimise corticosteroid exposure.
Herpes zoster
Recombinant zoster vaccine (Shingrix®) — 2 doses, ≥2 months apart. Can be given during immunosuppression (non-live vaccine). PBS-listed for immunocompromised patients ≥18 years.
PJP prophylaxis
Consider trimethoprim-sulfamethoxazole prophylaxis if on high-dose corticosteroids (≥20 mg/day prednisolone for ≥1 month) plus another immunosuppressant.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health
Disease burden
Aboriginal and Torres Strait Islander Australians experience a significantly higher burden of autoimmune disease, including rheumatic heart disease (virtually eliminated in non-Indigenous populations), higher rates of SLE, RA, and type 2 diabetes (which shares immunological overlap with autoimmune processes). SLE prevalence is estimated at 2–3× higher in Indigenous Australians. Rheumatic fever rates in remote Northern Territory communities remain among the highest in the world (AIHW, 2023).
Diagnostic delay
Delayed diagnosis is common due to limited specialist access in remote and very remote communities. Average time to rheumatology review in remote communities can exceed 6–12 months. Telehealth (MBS Items 91801, 91802) has improved access but does not replace the need for fly-in/fly-out specialist services and community-based Aboriginal health practitioners.
Access barriers
Geographic isolation limits access to specialist pathology (autoantibody panels), imaging (MRI for MS diagnosis), and biopsy services. PBS co-payment concessions are available for Aboriginal and Torres Strait Islander patients through the Closing the Gap PBS co-payment programme, reducing out-of-pocket medication costs to

📋 Key Information Summary

📋
  • Autoimmune diseases result from loss of immunological self-tolerance, with the immune system attacking host tissues via autoantibodies, immune complexes, or autoreactive T cells.
  • Australia has among the highest autoimmune disease prevalence globally, affecting approximately 5–8% of the population, with higher rates in Aboriginal and Torres Strait Islander communities.
  • Classification is divided into organ-specific (e.g., type 1 diabetes, Hashimoto thyroiditis, coeliac disease) and systemic (e.g., systemic lupus erythematosus, rheumatoid arthritis, systemic sclerosis) categories.
  • Pathogenesis involves a combination of genetic susceptibility (HLA associations), environmental triggers (infections, UV, smoking), epigenetic dysregulation, and failure of immune checkpoint mechanisms.
  • Diagnostic workup centres on clinical assessment, targeted autoantibody panels (ANA, anti-dsDNA, anti-CCP, anti-TPO), inflammatory markers (ESR, CRP), and histopathological confirmation where indicated.
  • Anti-nuclear antibody (ANA) testing has high sensitivity but low specificity for SLE; a positive ANA alone is insufficient for diagnosis — correlate with clinical features and specific extractable nuclear antigen (ENA) profiles.
  • Management follows a stepwise approach: symptomatic relief (NSAIDs, analgesics) → corticosteroid bridging → conventional DMARDs (methotrexate, hydroxychloroquine, azathioprine) → biologic DMARDs (TNF-α inhibitors, rituximab) → targeted synthetic DMARDs (JAK inhibitors).
  • Hydroxychloroquine (Plaquenil®) is PBS-listed for SLE and rheumatoid arthritis; requires baseline and annual ophthalmological screening for retinal toxicity after cumulative doses exceeding 1000 g.
  • Methotrexate (Methoblastin®) remains the anchor DMARD for RA; mandatory monitoring includes FBC, LFTs, and renal function every 2–4 weeks initially, then every 2–3 months at stable dose.
  • Biologic DMARDs require screening for latent tuberculosis (IGRA or tuberculin skin test), hepatitis B/C serology, and varicella status before initiation.
  • Immunosuppressive therapy significantly increases susceptibility to infections — pneumococcal, influenza, and COVID-19 vaccination should be optimised prior to commencing biologics.
  • Aboriginal and Torres Strait Islander peoples experience higher disease burden, delayed diagnosis, and poorer outcomes — culturally safe care, community-based follow-up, and PBS co-payment concessions are essential.
  • Pre-conception counselling is critical for women of childbearing age, as methotrexate, mycophenolate, and cyclophosphamide are teratogenic; hydroxychloroquine and azathioprine are considered safe in pregnancy.

Introduction & Australian Epidemiology

Autoimmune disease encompasses a broad spectrum of disorders in which the adaptive or innate immune system mounts an inappropriate response against self-antigens, resulting in chronic inflammation and tissue destruction. This failure of immunological self-tolerance may manifest as organ-specific disease — where a single organ is targeted — or as systemic disease with multi-organ involvement.

Australia has one of the highest prevalences of autoimmune disease in the world. An estimated 1.2 million Australians (approximately 5–8% of the population) live with one or more autoimmune conditions. Rheumatoid arthritis alone affects approximately 456,000 Australians, while systemic lupus erythematosus (SLE) disproportionately affects women of childbearing age at a ratio of approximately 9:1 (female to male). Type 1 diabetes, coeliac disease, autoimmune thyroiditis, and inflammatory bowel disease collectively represent the most common organ-specific autoimmune conditions encountered in Australian primary care.

⚠️
Australian burden: Autoimmune diseases are among the leading causes of chronic disability in Australians aged 15–44 years. The total economic burden exceeds billion annually, encompassing healthcare costs, lost productivity, and informal care needs (AIHW, 2023).

Key epidemiological observations in Australia include:

  • Rheumatoid arthritis prevalence is 1.9% in women and 0.8% in men, with higher rates in Aboriginal and Torres Strait Islander populations.
  • SLE prevalence in Australia is approximately 45 per 100,000, with significantly higher rates in Indigenous Australians, particularly those of mixed ancestry.
  • Type 1 diabetes incidence in Australian children (0–14 years) is approximately 23 per 100,000 per year — among the highest rates globally.
  • Coeliac disease affects approximately 1 in 70 Australians, though many remain undiagnosed; active case-finding is recommended in at-risk groups.
  • Autoimmune thyroiditis (Hashimoto disease) is the most common autoimmune condition in Australia, with a prevalence of 3–5%.
  • Geographic and climatic variations influence disease patterns — UV radiation exposure is a recognised trigger for SLE flares in northern Australia, while vitamin D deficiency in southern latitudes may modulate immune function.

Sex and Gender Considerations

Approximately 78% of individuals affected by autoimmune disease are female. Oestrogen promotes B-cell survival and antibody production, while X-chromosome inactivation mosaicism may contribute to greater immune diversity and self-reactivity. These sex-based differences have significant implications for screening, diagnosis, and management in Australian clinical practice.

Classification & Types

Autoimmune diseases are classified based on the target of immune attack and the breadth of organ involvement. This classification guides diagnostic workup, specialist referral pathways, and therapeutic strategies relevant to Australian practice.

Organ-Specific Autoimmune Diseases

In organ-specific autoimmune diseases, the immune response is directed against antigens confined to a single organ or tissue. These conditions are typically managed by organ-specific specialists in the Australian healthcare system.

Condition Target Organ Key Autoantibodies Typical Specialist Australian Prevalence
Hashimoto thyroiditis Thyroid Anti-TPO, anti-thyroglobulin Endocrinologist / GP 3–5%
Graves disease Thyroid TSH receptor antibodies (TRAb) Endocrinologist ~0.5%
Type 1 diabetes Pancreatic β cells Anti-GAD65, anti-IA-2, anti-ZnT8 Endocrinologist / Paediatrician ~0.5%
Coeliac disease Small bowel mucosa Anti-tTG IgA, anti-endomysial Gastroenterologist / GP ~1.4%
Autoimmune hepatitis Liver ANA, anti-SMA, anti-LKM-1 Gastroenterologist / Hepatologist ~24 per 100,000
Primary biliary cholangitis Intrahepatic bile ducts Anti-mitochondrial (AMA) Gastroenterologist / Hepatologist ~35 per 100,000
Multiple sclerosis CNS myelin Oligoclonal bands (CSF) Neurologist ~100 per 100,000
Myasthenia gravis Neuromuscular junction Anti-AChR, anti-MuSK Neurologist ~20 per 100,000
Autoimmune haemolytic anaemia Red blood cells Direct Coombs test positive Haematologist ~1–3 per 100,000/yr
Pemphigus vulgaris Skin / mucosal epithelium Anti-desmoglein 1 & 3 Dermatologist ~1–5 per 100,000

Systemic Autoimmune Diseases

Systemic autoimmune diseases involve immune-mediated damage to multiple organs and tissues, often through circulating autoantibodies, immune complex deposition, or widespread T-cell activation. These are predominantly managed by rheumatologists in collaboration with organ-specific specialists.

Condition Organs Affected Key Autoantibodies Hallmark Feature F:M Ratio
Systemic lupus erythematosus (SLE) Skin, joints, kidneys, brain, serosal surfaces ANA, anti-dsDNA, anti-Smith, anti-Ro/La Multi-system flares, nephritis 9:1
Rheumatoid arthritis (RA) Synovial joints (symmetric) RF, anti-CCP (ACPA) Symmetric polyarthritis, erosions 3:1
Systemic sclerosis (scleroderma) Skin, lungs, GI tract, vasculature Anti-Scl-70, anti-centromere, anti-RNA pol III Skin fibrosis, Raynaud, ILD / PAH 4:1
Sjögren syndrome Salivary, lacrimal glands, extraglandular Anti-Ro (SSA), anti-La (SSB), RF Sicca symptoms, fatigue 9:1
Systemic vasculitis (ANCA-associated) Small-to-medium vessels, kidneys, lungs c-ANCA (PR3), p-ANCA (MPO) GPA, MPA, EGPA subtypes 1:1
Dermatomyositis / Polymyositis Skeletal muscle, skin (dermatomyositis) Anti-Jo-1, anti-Mi-2, anti-MDA5 Proximal myopathy, heliotrope rash 2:1
Antiphospholipid syndrome Vascular endothelium (thrombotic) Anti-cardiolipin, anti-β2GP1, lupus anticoagulant Recurrent thrombosis, pregnancy loss 5:1

Mixed and Overlap Syndromes

A significant proportion of Australian patients present with features spanning multiple autoimmune categories. Overlap syndromes include:

  • Mixed connective tissue disease (MCTD): Features of SLE, systemic sclerosis, polymyositis, and RA with high-titre anti-U1 RNP antibodies.
  • Anti-synthetase syndrome: Myositis, interstitial lung disease, mechanic's hands, arthritis, Raynaud phenomenon, with anti-aminoacyl-tRNA synthetase antibodies.
  • Primary Sjögren syndrome with RA overlap: Common in clinical practice; requires integrated management of sicca symptoms and inflammatory arthritis.
  • Scleroderma-myositis overlap: Skin thickening with proximal muscle weakness; requires combined rheumatology and respiratory monitoring for interstitial lung disease.

Pathogenesis

The pathogenesis of autoimmune disease is multifactorial, involving an interplay between genetic predisposition, environmental triggers, immune dysregulation, and stochastic events. Understanding these mechanisms is essential for rational therapeutic targeting and risk stratification in Australian patients.

Failure of Central and Peripheral Tolerance

Immunological self-tolerance operates at two levels:

  • Central tolerance: In the thymus (T cells) and bone marrow (B cells), autoreactive lymphocytes are eliminated through negative selection. Defects in the AIRE (autoimmune regulator) gene impair thymic expression of peripheral tissue antigens, allowing autoreactive T cells to escape into the periphery. AIRE mutations cause autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED/APS-1).
  • Peripheral tolerance: Autoreactive lymphocytes that escape central deletion are controlled by regulatory T cells (Tregs, CD4+CD25+FoxP3+), anergy (functional unresponsiveness), and activation-induced cell death. Deficiency or dysfunction of Tregs is a hallmark of many autoimmune diseases.

Genetic Susceptibility

Genome-wide association studies (GWAS) have identified over 200 susceptibility loci for autoimmune disease. The HLA region on chromosome 6p21 remains the strongest genetic risk factor for most conditions:

Disease HLA Association Odds Ratio Non-HLA Genes
Rheumatoid arthritis HLA-DRB1 (shared epitope) 3–6 PTPN22, STAT4, CTLA4
SLE HLA-DR2, HLA-DR3 1.5–3 IRF5, STAT4, TNFAIP3, complement genes (C2, C4)
Type 1 diabetes HLA-DR3, HLA-DR4, HLA-DQ8 6–20 INS, PTPN22, IL2RA, CTLA4
Coeliac disease HLA-DQ2, HLA-DQ8 ~100 (necessary but not sufficient) SH2B3, IL18RAP, TAGAP
Ankylosing spondylitis HLA-B27 ~100 ERAP1, IL23R, IL12B
Multiple sclerosis HLA-DRB1*15:01 3 IL7R, IL2RA, CD58
ℹ️
Australian context: HLA-B27 prevalence in the general Australian population is approximately 8–10%, but rises to 20–25% in Aboriginal and Torres Strait Islander populations, contributing to higher rates of spondyloarthropathy in these communities.

Environmental Triggers

Environmental factors are critical in initiating or exacerbating autoimmune disease in genetically susceptible individuals. Triggers with particular relevance in the Australian context include:

  • Ultraviolet radiation: Australia's high UV index (particularly northern latitudes) is a well-established trigger for SLE flares, inducing keratinocyte apoptosis and exposing intracellular autoantigens. UVB also modulates dendritic cell function and promotes type I interferon production.
  • Infections (molecular mimicry): Streptococcal pharyngitis triggers rheumatic heart disease; EBV is strongly associated with SLE and MS; Campylobacter jejuni triggers Guillain-Barré syndrome; hepatitis C is linked to cryoglobulinaemic vasculitis. Molecular mimicry occurs when microbial peptides share structural homology with self-antigens.
  • Smoking: Cigarette smoking is the strongest modifiable environmental risk factor for seropositive RA (anti-CCP positive), increasing risk 2–3-fold, particularly in HLA-DRB1 shared epitope carriers. Smoking also exacerbates SLE and Graves disease.
  • Silica and organic solvents: Occupational silica dust exposure (mining, construction) increases RA and SLE risk — relevant to Australia's resource sector. Organic solvents are associated with systemic sclerosis.
  • Vitamin D: Vitamin D deficiency, prevalent in southern Australian states during winter, modulates immune function and has been epidemiologically linked to increased MS and type 1 diabetes incidence. Optimal 25-hydroxyvitamin D levels ≥75 nmol/L are recommended.
  • Gut microbiome: Dysbiosis (reduced Firmicutes, increased Bacteroidetes) is implicated in RA, SLE, and IBD. Diet, antibiotic exposure, and geographic factors shape the microbiome in Australian populations.
  • Hormonal factors: Oestrogen upregulates B-cell activating factor (BAFF) and promotes class-switch recombination. Pregnancy modulates disease activity (RA improves in pregnancy but SLE may flare). Postpartum flares are common across many autoimmune conditions.

Immunopathological Mechanisms

Tissue damage in autoimmune disease is mediated through four classical mechanisms (Gell & Coombs classification):

Type II
Cytotoxic
Autoantibodies bind cell-surface antigens, triggering complement activation, ADCC, or direct functional interference.
Example: autoimmune haemolytic anaemia, Goodpasture syndrome, Graves disease (stimulatory)
Type III
Immune Complex
Circulating antigen-antibody complexes deposit in tissues (kidney, skin, joints), activating complement and recruiting neutrophils.
Example: SLE nephritis, serum sickness, ANCA-associated vasculitis
Type IV
Delayed-Type Hypersensitivity
Autoreactive CD4+ Th1/Th17 cells and CD8+ cytotoxic T cells directly damage tissue through cytokine release and cytotoxic granules.
Example: type 1 diabetes, rheumatoid arthritis, multiple sclerosis, Hashimoto thyroiditis

The Cytokine Network in Autoimmunity

Cytokine dysregulation is central to autoimmune pathogenesis and provides the molecular basis for biologic DMARD therapy. Key cytokine pathways targeted by current and emerging therapies include:

  • TNF-α: Pro-inflammatory cytokine central to RA, IBD, psoriasis, and spondyloarthropathy pathogenesis. Targeted by adalimumab (Humira®), etanercept (Enbrel®), infliximab (Remicade®).
  • IL-6: Drives acute-phase response, B-cell differentiation, and Th17 differentiation. Targeted by tocilizumab (Actemra®) and sarilumab (Kevzara®).
  • IL-17: Produced by Th17 cells; promotes neutrophil recruitment and tissue inflammation in psoriasis, spondyloarthropathy, and RA. Targeted by secukinumab (Cosentyx®) and ixekizumab (Taltz®).
  • IL-23: Drives Th17 cell maintenance and expansion. Targeted by guselkumab (Tremfya®) and risankizumab (Skyrizi®).
  • Type I interferons (IFN-α/β): Plasmacytoid dendritic cell overproduction of IFN-α is a hallmark of SLE. Targeted by anifrolumab (Saphnelo®), now TGA-approved in Australia for SLE.
  • BAFF (B-cell activating factor): Promotes B-cell survival and is elevated in SLE. Targeted by belimumab (Benlysta®).
  • JAK-STAT pathway: Intracellular signalling cascade downstream of multiple cytokine receptors. Targeted by tofacitinib (Xeljanz®), baricitinib (Olumiant®), upadacitinib (Rinvoq®).

Diagnostic Approach

The diagnostic approach to autoimmune disease requires integration of clinical assessment, serological testing, imaging, and histopathology. A systematic approach is essential to avoid diagnostic delay, which remains a significant issue in Australia — average time to diagnosis for conditions such as SLE and systemic sclerosis is 2–6 years from symptom onset.

Clinical Assessment

A thorough history and examination should focus on:

  • Symptom pattern: Duration, distribution (symmetric vs. asymmetric), chronicity, and systemic features (fatigue, weight loss, fevers, night sweats).
  • Organ-specific enquiry: Joint pain/swelling, skin rashes, Raynaud phenomenon, sicca symptoms, oral ulcers, alopecia, dysphagia, chest pain (serositis), visual changes, neurological symptoms.
  • Family history: Autoimmune diseases cluster in families; ~30% of patients with one autoimmune condition will develop another (polyautoimmunity).
  • Medication history: Drug-induced lupus (hydralazine, procainamide, isoniazid, minocycline) must be excluded.
  • Reproductive history: Recurrent miscarriage may indicate antiphospholipid syndrome.
  • Occupational and environmental exposures: Smoking, silica dust, solvents, UV exposure.

Laboratory Investigations

Tier 1 — Screening (GP-accessible, MBS-rebatable)

Available
Full blood count (FBC)
Cytopenias (anaemia of chronic disease, autoimmune haemolytic anaemia, thrombocytopenia, leucopenia) — MBS Item 65070.
Available
ESR and CRP
Non-specific inflammatory markers. ESR elevated in SLE, RA flares; CRP often normal in SLE unless serositis/infection. MBS Item 65070.
Available
Renal function and urinalysis
Creatinine, eGFR, urine ACR — screen for lupus nephritis, ANCA vasculitis renal involvement. MBS Item 66500.
Available
Liver function tests
Hepatocellular vs. cholestatic pattern — screen for autoimmune hepatitis, PBC. MBS Item 66515.
Available
ANA (anti-nuclear antibody) by IIF
Screening test for SLE, Sjögren, scleroderma, MCTD. Sensitivity ~95% for SLE but specificity ~50%. Titre ≥1:160 considered clinically significant. Note: Low-titre ANA (≤1:80) is present in ~15% of healthy Australians and does not indicate autoimmune disease. MBS Item 69300.
Available
Rheumatoid factor (RF) and anti-CCP
Anti-CCP has specificity >95% for RA and is more specific than RF. Double seropositivity (RF+ and anti-CCP+) predicts erosive disease. MBS Item 69306.

Tier 2 — Specialist-directed

Specialist
Extractable nuclear antigen (ENA) panel
Anti-dsDNA (SLE-specific, correlates with nephritis activity), anti-Smith (SLE-specific but low sensitivity), anti-Ro/La (Sjögren, neonatal lupus), anti-U1 RNP (MCTD), anti-Scl-70 (diffuse scleroderma). Recommended when ANA ≥1:160 with clinical suspicion.
Specialist
Complement levels (C3, C4, CH50)
Low C3 and C4 in active SLE (immune complex consumption); isolated C4 deficiency predisposes to SLE.
Specialist
ANCA (c-ANCA/PR3, p-ANCA/MPO)
ANCA-associated vasculitis screening — GPA (c-ANCA/PR3), MPA and EGPA (p-ANCA/MPO). Performed by ELISA after positive IIF screening.
Specialist
Antiphospholipid antibodies
Lupus anticoagulant, anti-cardiolipin IgG/IgM, anti-β2 glycoprotein I. Must be positive on two occasions ≥12 weeks apart for APS diagnosis. Essential in unexplained thrombosis or recurrent pregnancy loss.
Specialist
Cryoglobulins
Type I (haematological), Type II/III (mixed, associated with hepatitis C, SLE). Sample must be kept at 37°C until laboratory processing.
Specialist
Muscle-specific antibodies
Anti-AChR, anti-MuSK, anti-LRP4 — myasthenia gravis. Anti-Jo-1, anti-Mi-2, anti-MDA5 — inflammatory myopathies.

Histopathology

Tissue biopsy remains the gold standard for diagnosing and staging several autoimmune conditions:

  • Renal biopsy: ISN/RPS classification of lupus nephritis (Class I–VI) guides treatment intensity. Repeat biopsy warranted for suspected transformation or treatment failure.
  • Skin biopsy: Direct immunofluorescence (lupus band test), histopathology for vasculitis, pemphigus/pemphigoid subtyping.
  • Small bowel biopsy: Villous atrophy, crypt hyperplasia, intraepithelial lymphocytosis (Marsh classification) in coeliac disease — though diagnosis may be made without biopsy in children with tTG IgA >10× ULN and positive EMA.
  • Salivary gland biopsy: Minor salivary gland biopsy (focus score ≥1) supports Sjögren syndrome diagnosis when serology is equivocal.
  • Liver biopsy: Interface hepatitis with plasma cell infiltrate in autoimmune hepatitis; staging guides treatment decisions.

Classification Criteria

Validated classification criteria assist in standardising diagnosis and facilitating clinical trial recruitment. Key criteria sets used in Australian practice include:

  • SLE: 2019 EULAR/ACR classification criteria (ANA ≥1:80 entry criterion, then additive weighted domains; ≥10 points = classified as SLE).
  • RA: 2010 ACR/EULAR classification criteria (joint involvement, serology, acute-phase reactants, symptom duration; ≥6/10 points = classified as RA).
  • Systemic sclerosis: 2013 ACR/EULAR criteria (skin thickening of fingers extending proximal to MCPs as sufficient criterion, or ≥9 points from 7 items).
  • ANCA-associated vasculitis: 2022 ACR/EULAR classification criteria for GPA, MPA, and EGPA.
  • Sjögren syndrome: 2016 ACR/EULAR criteria (anti-Ro positivity, focal lymphocytic sialadenitis, ocular staining score, Schirmer test, salivary flow; ≥4 points).
⚠️
Diagnostic pitfall: A positive ANA is not synonymous with autoimmune disease. Up to 15% of healthy Australians have a low-titre ANA. Do not order ANA as a general screen for fatigue or non-specific musculoskeletal symptoms — this leads to patient anxiety, unnecessary referrals, and healthcare costs. Order ANA only when clinical features suggest a specific connective tissue disease.

Referral Pathways in Australia

Clinical Scenario Referral Urgency
Inflammatory polyarthritis (suspected RA) Rheumatologist Within 6 weeks of symptom onset (treat-to-target)
Suspected SLE with renal involvement Rheumatologist + Nephrologist Urgent (days)
Suspected ANCA vasculitis Rheumatologist / Nephrologist Emergency (same day)
New-onset type 1 diabetes Endocrinologist / Paediatrician Urgent (1–2 days)
Suspected coeliac disease Gastroenterologist Routine (4–6 weeks)
New neurological deficit (MS suspected) Neurologist Urgent (1–2 weeks)

Management Principles

Management of autoimmune disease is guided by the principles of treat-to-target, stepwise immunosuppression, multidisciplinary care, and individualised risk-benefit assessment. The therapeutic armamentarium in Australia has expanded significantly with the PBS listing of biologic and targeted synthetic DMARDs.

General Therapeutic Principles

  • Treat to target: Aim for remission or low disease activity using validated composite measures (DAS28 for RA, SLEDAI-2K for SLE, CDAI/LDA). Reassess at 3–6 month intervals.
  • Step-up approach: Start with conventional synthetic DMARDs; escalate to biologic or targeted synthetic DMARDs if target not achieved.
  • Early intervention: Window-of-opportunity concept in RA — initiation of DMARD within 3 months of symptom onset improves long-term outcomes.
  • Combination therapy: Combining DMARDs (e.g., methotrexate + hydroxychloroquine + sulfasalazine) may be more effective than monotherapy in RA, with acceptable safety.
  • Bridging corticosteroids: Low-dose prednisolone (≤7.5 mg/day) or intramuscular methylprednisolone for acute flares; taper to minimum effective dose within 3–6 months.
  • Multidisciplinary care: Rheumatologist, GP, physiotherapist, occupational therapist, psychologist, podiatrist, and specialist nurse — coordinated through GP management plans (GPMP/TCA).

Pharmacological Therapy

Conventional Synthetic DMARDs

💊
Methotrexate
Methoblastin® · Antimetabolite (folate antagonist)
Adult dose Start 7.5–10 mg PO/SC once weekly; titrate to 15–25 mg/week. Co-prescribe folic acid 5 mg weekly (not on methotrexate day).
Paediatric dose JIA: 10–15 mg/m²/week PO/SC; max 25 mg/week.
Renal adjustment eGFR <30 mL/min: avoid. eGFR 30–59: reduce dose 50%.
Hepatic adjustment Avoid in significant hepatic impairment or active hepatitis B/C.
Monitoring FBC, LFTs, renal function — every 2 weeks × 6 weeks, then every 2–3 months.
PBS status ✔ PBS General Benefit
💊
Hydroxychloroquine
Plaquenil® · Generic · Antimalarial / immunomodulator
Adult dose 200–400 mg daily (≤5 mg/kg actual body weight).
Paediatric dose 3–5 mg/kg/day; max 400 mg/day.
Renal adjustment eGFR <30 mL/min: reduce dose.
Key adverse effects Retinal toxicity (cumulative risk after >1000 g total dose). Baseline ophthalmology exam + annual screening after 5 years (or sooner if risk factors).
PBS status ✔ PBS General Benefit
💊
Azathioprine
Imuran® · Purine antimetabolite
Adult dose Start 50 mg daily; titrate to 2–2.5 mg/kg/day based on response and TPMT status.
Key consideration Check TPMT/NUDT15 genotype before initiation. TPMT-deficient patients: avoid or drastically reduce dose.
Monitoring FBC every 1–2 weeks for first 8 weeks, then every 3 months. LFTs periodically.
PBS status ✔ PBS General Benefit
💊
Mycophenolate mofetil
CellCept® · Generic · Inosine monophosphate dehydrogenase inhibitor
Adult dose Start 500 mg BD; titrate to 1–1.5 g BD. Used for lupus nephritis, autoimmune hepatitis, vasculitis maintenance.
Key warning Teratogenic — Category X. Reliable contraception mandatory during and for 6 weeks after discontinuation.
PBS status ✔ PBS Restricted Benefit

Biologic DMARDs

⚠️
Pre-biologic screening checklist (mandatory):
  • Tuberculosis screening: IGRA (QuantiFERON-TB Gold or T-SPOT) or tuberculin skin test. Treat latent TB with 3 months isoniazid + rifapentine (3HP) or 6–9 months isoniazid before biologic initiation.
  • Hepatitis B serology (HBsAg, anti-HBc, anti-HBs). If HBsAg positive: antiviral prophylaxis (entecavir/tenofovir) before and during biologic therapy.
  • Hepatitis C serology. Active infection: treat to SVR before biologic initiation where possible.
  • Vaccination update: pneumococcal (Prevenar 13® + Pneumovax 23®), influenza, COVID-19, herpes zoster (Shingrix®). Live vaccines contraindicated on biologics.
  • Baseline bloods: FBC, LFTs, renal function, lipids (for JAK inhibitors).
💉
Adalimumab
Humira® · Biosimilars available (Hadlima®, Hyrimoz®, Idacio®) · Anti-TNF-α
Adult dose 40 mg SC every 2 weeks. Can increase to weekly in RA.
Indications (PBS) RA, AS, PsA, Crohn disease, ulcerative psoriasis, hidradenitis suppurativa, uveitis.
PBS status Authority Required
💉
Rituximab
MabThera® · Biosimilars available · Anti-CD20 (B-cell depletion)
Adult dose 1000 mg IV on days 1 and 15. Repeat cycle every 6 months based on disease activity.
Key indications RA (inadequate response to TNF inhibitor), ANCA vasculitis, refractory SLE.
PBS status Authority Required
💉
Belimumab
Benlysta® · Anti-BAFF/BLyS
Adult dose 10 mg/kg IV every 4 weeks (after loading at weeks 0, 2, 4) or 200 mg SC weekly.
Key indication Active SLE (SLEDAI ≥6) despite standard therapy; also approved for lupus nephritis.
PBS status Authority Required
💊
Tofacitinib
Xeljanz® · JAK1/JAK3 inhibitor
Adult dose 5 mg PO BD (RA, PsA, UC) or 11 mg SR daily.
Key safety Increased risk of VTE, MACE, and malignancy (particularly in patients >65 years and cardiovascular risk factors). Cardiovascular risk assessment mandatory before initiation.
PBS status Authority Required

Non-Pharmacological Management

  • Patient education and self-management: Structured programmes improve adherence and outcomes. Arthritis Australia provides educational resources.
  • Exercise: Regular moderate exercise (150 minutes/week) improves fatigue, cardiovascular fitness, and psychological well-being without worsening disease activity.
  • Diet: Mediterranean-style diet associated with reduced inflammatory markers in RA. Strict gluten-free diet is the only treatment for coeliac disease.
  • Smoking cessation: Absolute priority — smoking worsens RA, SLE, Graves disease, and MS. Offer NRT, varenicline, or bupropion as per RACGP guidelines.
  • Psychological support: Depression and anxiety prevalence is 2–3× higher in autoimmune disease. Cognitive behavioural therapy and acceptance and commitment therapy are recommended.
  • Vaccination: All patients should receive pneumococcal, influenza (annually), COVID-19, and herpes zoster vaccines. Live vaccines (MMR, varicella, yellow fever) should be administered ≥4 weeks before starting immunosuppression.
  • Cardiovascular risk management: Autoimmune disease is an independent cardiovascular risk factor. Aggressive management of hypertension, dyslipidaemia, and diabetes is essential. Use the modified CVD risk calculator incorporating disease activity.

Monitoring Framework

Parameter Frequency Purpose
Disease activity indices (DAS28, SLEDAI-2K, BASDAI) Every 1–3 months until target, then every 3–6 months Treat-to-target assessment
FBC Every 2–4 weeks initially, then every 2–3 months Drug toxicity (cytopenias)
LFTs Every 2–4 weeks initially, then every 2–3 months Methotrexate hepatotoxicity
Renal function + urinalysis Every 3–6 months Lupus nephritis, drug nephrotoxicity
Ophthalmology (hydroxychloroquine) Baseline + annual after 5 years (or earlier with risk factors) Retinal toxicity screening
Dual-energy X-ray absorptiometry (DEXA) Baseline if corticosteroid use ≥3 months; then every 1–2 years Glucocorticoid-induced osteoporosis
Lipid profile Before JAK inhibitor; then annually Cardiovascular risk (JAK inhibitor effect on lipids)
🚨
Safety-critical: Methotrexate is teratogenic (FDA Category X / Australian Category D). It must be discontinued at least 3 months before conception in both men and women. Adequate contraception is mandatory during treatment. Hydroxychloroquine and azathioprine are considered safe in pregnancy and should be continued to maintain remission.

Special Populations

🤰
Pregnancy
Safe to continue
Hydroxychloroquine, azathioprine (dose ≤2 mg/kg/day), tacrolimus, sulfasalazine (with folate), low-dose prednisolone.
Contraindicated — stop ≥3 months pre-conception
Methotrexate, mycophenolate mofetil, cyclophosphamide, leflunomide (requires cholestyramine washout), warfarin.
Specialist guidance required
Biologics — certolizumab pegol (Cimzia®) preferred as minimal placental transfer; other TNF inhibitors can be used until 2nd trimester. Rituximab: avoid if possible. JAK inhibitors: contraindicated.
Key considerations
Anti-Ro/La antibodies: risk of neonatal lupus (congenital heart block, neonatal rash) — foetal echocardiography from 16 weeks. Antiphospholipid syndrome: low-dose aspirin + LMWH throughout pregnancy.
👶
Paediatrics
Juvenile idiopathic arthritis (JIA)
Most common paediatric rheumatic disease in Australia (~1 per 1000 children). Methotrexate is first-line systemic DMARD. Biologics: etanercept and adalimumab are PBS-listed for polyarticular JIA ≥4 years.
Paediatric SLE
More aggressive than adult-onset; higher rates of nephritis and neuropsychiatric involvement. Hydroxychloroquine + mycophenolate or cyclophosphamide for nephritis.
Type 1 diabetes
Rising incidence in Australian children. Teplizumab (Tzield®) — anti-CD3 — now TGA-approved for stage 2 T1D (autoantibodies + dysglycaemia) to delay onset. Continuous glucose monitoring (CGM) funded through NDSS for all Australians with T1D.
👴
Elderly (≥65 years)
Late-onset RA
Often seronegative; differential includes polymyalgia rheumatica (PMR). Lower methotrexate starting dose (5–7.5 mg/week). Biologics: higher infection risk; screen more aggressively for TB and malignancy.
Corticosteroid caution
Accelerated osteoporosis, diabetes, cataracts, myopathy. If on prednisolone ≥3 months: bisphosphonate prophylaxis (alendronate 70 mg weekly, PBS General Benefit).
JAK inhibitors
Increased VTE and MACE risk in patients ≥65 years — avoid tofacitinib as first-line in this age group.
🫘
Renal Impairment
Methotrexate
eGFR <30 mL/min: contraindicated. eGFR 30–59: reduce dose 50%. Monitor more frequently.
Cyclophosphamide
Dose reduction required in renal impairment (GFR-based dosing per Euro-Lupus or NIH protocols). Mesna co-administration to prevent haemorrhagic cystitis.
NSAIDs
Avoid in eGFR <30 mL/min. Contribute to AKI, hyperkalaemia, and interstitial nephritis.
Rituximab
No dose adjustment; safe in dialysis patients. Monitor for delayed neutropenia.
🫁
Hepatic Impairment
Methotrexate
Avoid in active hepatitis B/C, significant hepatic fibrosis, or heavy alcohol use. Serial FibroScan if prolonged use.
Leflunomide
Hepatotoxic — contraindicated in significant liver disease. Monitor LFTs monthly for first 6 months.
Biologics
Generally safe in liver disease. Screen for hepatitis B reactivation risk; antiviral prophylaxis if HBsAg positive.
🦠
Immunocompromised
Infection risk
Combination immunosuppression (e.g., methotrexate + biologic + corticosteroids) triples serious infection risk. Aim to minimise corticosteroid exposure.
Herpes zoster
Recombinant zoster vaccine (Shingrix®) — 2 doses, ≥2 months apart. Can be given during immunosuppression (non-live vaccine). PBS-listed for immunocompromised patients ≥18 years.
PJP prophylaxis
Consider trimethoprim-sulfamethoxazole prophylaxis if on high-dose corticosteroids (≥20 mg/day prednisolone for ≥1 month) plus another immunosuppressant.

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health
Disease burden
Aboriginal and Torres Strait Islander Australians experience a significantly higher burden of autoimmune disease, including rheumatic heart disease (virtually eliminated in non-Indigenous populations), higher rates of SLE, RA, and type 2 diabetes (which shares immunological overlap with autoimmune processes). SLE prevalence is estimated at 2–3× higher in Indigenous Australians. Rheumatic fever rates in remote Northern Territory communities remain among the highest in the world (AIHW, 2023).
Diagnostic delay
Delayed diagnosis is common due to limited specialist access in remote and very remote communities. Average time to rheumatology review in remote communities can exceed 6–12 months. Telehealth (MBS Items 91801, 91802) has improved access but does not replace the need for fly-in/fly-out specialist services and community-based Aboriginal health practitioners.
Access barriers
Geographic isolation limits access to specialist pathology (autoantibody panels), imaging (MRI for MS diagnosis), and biopsy services. PBS co-payment concessions are available for Aboriginal and Torres Strait Islander patients through the Closing the Gap PBS co-payment programme, reducing out-of-pocket medication costs to

📋 Key Information Summary

📋
  • Angioedema is transient, localised swelling of deep dermis, subcutaneous tissue, or submucosa; laryngeal involvement is a medical emergency with risk of fatal asphyxiation.
  • Two principal pathophysiological pathways: histamine-mediated (allergic / mast-cell) and bradykinin-mediated (hereditary angioedema, ACE-inhibitor induced).
  • Histamine-mediated angioedema typically responds to adrenaline, H₁-antihistamines, and corticosteroids; bradykinin-mediated angioedema does not — misdiagnosis delays effective treatment.
  • Hereditary angioedema (HAE) is caused by C1-inhibitor deficiency (Type I ~85 %, Type II ~15 %); Type III (normal C1-INH) is rarer and often factor-XII mutation–related.
  • ACE-inhibitor angioedema accounts for 20–40 % of emergency angioedema presentations in Australia; onset may occur months to years after commencing therapy.
  • First-episode or diagnostic uncertainty requires C4 level as screening test — if low, proceed to C1-inhibitor quantitative and functional assays.
  • Emergency airway management takes precedence; early anaesthetic/ENT review if any stridor, voice change, or tongue swelling.
  • For histamine-mediated attacks: adrenaline 0.01 mg/kg IM (max 0.5 mg), IV dexchlorpheniramine or promethazine, hydrocortisone IV.
  • For HAE acute attacks: C1-inhibitor concentrate (Berinert®) IV or icatibant (Firazyr®) SC — both available through special-access pathways in Australia.
  • ACE inhibitors must be permanently discontinued after an angioedema episode; switch to ARB or alternative with monitoring.
  • All patients with confirmed HAE should carry a personalised action plan and medical-alert identification; consider long-term prophylaxis with danazol, tranexamic acid, or subcutaneous C1-INH (Haegarda®).
  • Aboriginal and Torres Strait Islander peoples may face delayed presentation due to geographic remoteness; ensure culturally safe follow-up and access to adrenaline autoinjectors.

Introduction & Australian Epidemiology

Angioedema is characterised by transient, localised subcutaneous or submucosal swelling resulting from increased vascular permeability in deep tissue layers. Unlike urticaria, which affects superficial dermis, angioedema involves deeper structures and presents with non-pitting, asymmetrical swelling — most commonly of the lips, tongue, periorbital region, and extremities. Involvement of the upper airway constitutes a life-threatening emergency that demands immediate recognition and intervention.

In Australia, angioedema accounts for an estimated 1 in 500 emergency department (ED) presentations annually, with hospital admission rates for angioedema rising by approximately 2–3 % per year over the past decade. The increasing prevalence is attributed in part to widespread ACE-inhibitor prescribing — ACE inhibitors are among the most commonly dispensed medications on the Pharmaceutical Benefits Scheme (PBS), and ACE-inhibitor angioedema now represents 20–40 % of all angioedema ED presentations nationally.

Hereditary angioedema (HAE) is rare, with an estimated prevalence of 1 in 50,000 Australians; however, significant diagnostic delay (averaging 8–10 years from first symptom to diagnosis) suggests under-recognition. The Australian HAE patient registry data indicate that patients experience a mean of 4–6 attacks per year before commencing prophylaxis, with laryngeal involvement reported in up to 50 % of patients over their lifetime.

This guideline covers the classification, pathophysiology, diagnosis, and emergency management of angioedema in the Australian clinical context, with attention to PBS-listed therapies, state-based hospital protocols, and equity considerations for underserved populations.

Angioedema clinical infographic — pathophysiology, clinical clues, diagnosis, imaging, and management
Tap or click image to enlarge — Angioedema: pathophysiology, clinical clues, diagnosis, imaging, and management.
Angioedema infographic, full size

Types of Angioedema

Accurate classification is essential because histamine-mediated and bradykinin-mediated angioedema require fundamentally different treatments. The major types encountered in Australian practice are summarised below.

Type Mechanism Common Triggers / Associations Responds to Adrenaline / Antihistamines?
Allergic (histamine-mediated) IgE-mediated mast-cell degranulation → histamine release Foods (peanut, shellfish, egg), NSAIDs, latex, insect stings, antibiotics (penicillin) Yes — first-line
Hereditary angioedema (HAE) Type I Quantitative C1-inhibitor deficiency → unregulated kallikrein → excess bradykinin Trauma, stress, dental procedures, OCP/oestrogens; often spontaneous No
HAE Type II Dysfunctional C1-inhibitor (normal or elevated levels, reduced function) Same as Type I No
HAE Type III (normal C1-INH) Often factor-XII gain-of-function mutation; oestrogen-sensitive Oestrogen-containing contraceptives, pregnancy No
ACE-inhibitor angioedema Bradykinin accumulation due to reduced degradation (ACE = kininase II) Enalapril, ramipril, perindopril — may occur months–years after initiation No
Acquired C1-inhibitor deficiency Autoantibody consumption of C1-INH; associated with lymphoproliferative disorders B-cell lymphoma, monoclonal gammopathy No
Idiopathic Unknown; may be histamine-mediated or bradykinin-mediated Diagnosis of exclusion Variable
⚠️
Critical distinction: Giving adrenaline, antihistamines, and corticosteroids to a patient with bradykinin-mediated angioedema (HAE or ACE-inhibitor) is ineffective and may delay appropriate therapy. Always consider bradykinin aetiology — especially if the tongue is involved without urticaria, or there is a family history or ACE-inhibitor use.

Pathophysiology

Histamine-Mediated (Allergic) Pathway

Allergen cross-links surface-bound IgE on mast cells and basophils, triggering degranulation and release of histamine, tryptase, prostaglandins, and leukotrienes. Histamine acts on H₁-receptors on vascular endothelial cells, causing endothelial cell contraction, intercellular gap formation, and plasma extravasation into the deep dermis and submucosa. The result is non-pitting oedema that is typically pruritic, often accompanied by urticaria, and resolves within 24–72 hours.

Bradykinin-Mediated Pathway

Bradykinin is a potent vasoactive nonapeptide generated by the action of kallikrein on high-molecular-weight kininogen (HMWK). C1-inhibitor (C1-INH) is the primary regulatory serine protease inhibitor (serpin) of this pathway — it inhibits activated factor XII (Hageman factor), plasma kallikrein, and C1s/C1r in the classical complement pathway.

In HAE Type I (~85 % of cases), reduced synthesis of C1-INH protein leads to uninhibited kallikrein activity and excess bradykinin production. In Type II (~15 %), C1-INH protein levels are normal or elevated but the molecule is dysfunctional. In both types, C4 is chronically low because of unregulated classical-pathway consumption.

ACE-inhibitor angioedema occurs because angiotensin-converting enzyme (ACE) is identical to kininase II — the primary enzyme responsible for bradykinin degradation. Inhibition of ACE raises local bradykinin concentrations, predisposing to angioedema. Individual susceptibility likely depends on polymorphisms in aminopeptidase P and neprilysin (alternative bradykinin-degradation pathways).

🔬
Bradykinin acts on endothelial B₂-receptors (constitutive; blocked by icatibant) and B₁-receptors (inducible; upregulated by inflammation). Current targeted therapies exploit these receptors or replace deficient C1-INH.

Clinical Features & Diagnosis

Clinical Presentation

Angioedema presents with recurrent episodes of localised, non-pitting oedema affecting one or more of the following sites:

  • Face: Lips, periorbital region, cheeks — the most common site overall
  • Upper airway: Tongue, uvula, soft palate, larynx — potentially fatal; 25–50 % of HAE patients experience at least one laryngeal attack
  • Extremities: Hands, feet — can be debilitating and interfere with daily function
  • Gastrointestinal tract: Colicky abdominal pain, nausea, vomiting, diarrhoea — due to bowel-wall oedema; may mimic an acute abdomen
  • Urogenital: Genital swelling (more common in HAE)

Differentiating Histamine-Mediated from Bradykinin-Mediated Angioedema

Feature Histamine-Mediated Bradykinin-Mediated (HAE / ACE-I)
Urticaria Usually present (≥ 90 %) Absent
Pruritus Prominent Usually absent; may have tingling / tightness
Prodrome None or sudden onset Tingling, erythema marginatum (serpiginous, non-pruritic rash) in ~40 % of HAE
Onset to peak Minutes to 1–2 hours Gradual over 12–36 hours; untreated lasts 2–5 days
Response to adrenaline Rapid improvement Poor or absent
Family history Atopy Autosomal dominant (50 %); 25 % are de-novo mutations
Medications NSAIDs, antibiotics ACE inhibitors, oestrogens

Diagnostic Approach

The diagnostic algorithm depends on clinical context:

1
Clinical Assessment
History of urticaria, medications (ACE inhibitors, OCP), family history, recurrence pattern, age of first episode. Document all medications including over-the-counter and herbal products.
2
First-Line Blood Tests
Serum C4 level — universally low in HAE Types I and II (even between attacks). If C4 is normal, bradykinin-mediated HAE is effectively excluded. If C4 is low, proceed to Step 3.
3
C1-Inhibitor Assays
C1-INH antigenic level (quantitative) and C1-INH functional assay. Type I: low level + low function. Type II: normal/high level + low function. Both assays should be performed simultaneously. Available at major Australian reference laboratories (Sullivan Nicolaides, Douglass Hanly Moir, Melbourne Pathology).
4
If C1-INH Normal — Consider
HAE Type III (normal C1-INH): genetic testing for F12 (factor XII) mutations, available through specialist referral (Clinical Immunology). Acquired C1-INH deficiency: C1q level (low in acquired, normal in hereditary).

Investigations with Australian Availability

Available Serum C4 MBS item 65070 · Turnaround: 1–3 days · Screening test for all suspected bradykinin angioedema
Available C1-INH quantitative level MBS item 65095 · Reference lab assay · Confirmatory for HAE Type I vs II
Available C1-INH functional assay Specialist pathology request · Essential alongside quantitative level
Specialist C1q level Differentiates acquired (low C1q) from hereditary (normal C1q) C1-INH deficiency
Specialist F12 gene mutation testing Referred to clinical genetics / immunology · For suspected HAE Type III
Available Serum tryptase Collect within 1–2 hours of symptom onset · Elevated in mast-cell-mediated reactions; normal in bradykinin-mediated

Emergency Management

🚨
Airway first: Any signs of upper-airway compromise (stridor, hoarseness, dyspnoea, tongue or uvula swelling) require immediate senior anaesthetic and/or ENT review. Do not delay intubation — progressive oedema may make intubation impossible within minutes. Have a surgical airway kit (cricothyroidotomy) at the bedside.

Immediate Resuscitation (All Angioedema Types)

1
Airway Assessment
Assess for stridor, voice change, inability to swallow secretions, tongue protrusion. Continuous SpO₂ monitoring. Call for senior help early — do not wait for deterioration.
2
High-Flow Oxygen
15 L/min via non-rebreather mask. Aim SpO₂ ≥ 94 %.
3
IV Access & Monitoring
Two large-bore IV cannulae. Continuous cardiac monitoring, BP every 5 minutes. Prepare for potential intubation or surgical airway.

Histamine-Mediated (Allergic) Angioedema — Acute Treatment

💉
Adrenaline (Epinephrine)
EpiPen® / Anapen® · Sympathomimetic
Adult dose 0.3–0.5 mg IM into anterolateral thigh (1:1000 = 1 mg/mL). Repeat every 5–15 min PRN.
Paediatric dose 0.01 mg/kg IM (max 0.3 mg in children < 30 kg; 0.5 mg if ≥ 30 kg)
Route Intramuscular (IM)
PBS status ✔ PBS General Benefit
💊
Dexchlorpheniramine
Polaramine® · H₁-antihistamine
Adult dose 5 mg IV/IM slow injection, repeat 6-hourly
Paediatric dose 0.125 mg/kg IV/IM (max 5 mg) 6-hourly
PBS status ✔ PBS General Benefit
💊
Hydrocortisone
Solu-Cortef® · Corticosteroid
Adult dose 200 mg IV bolus
Paediatric dose 4 mg/kg IV (max 200 mg)
PBS status ✔ PBS General Benefit

Bradykinin-Mediated Angioedema (HAE) — Acute Treatment

Standard allergy therapies (adrenaline, antihistamines, corticosteroids) are not effective for bradykinin-mediated attacks. Targeted therapies are required and should be administered as early as possible.

💉
C1-Inhibitor Concentrate (Human Plasma-Derived)
Berinert® · 500 IU vial · Replacement therapy
Adult dose 20 IU/kg IV over 10 minutes; max 100 IU/kg/day
Paediatric dose 20 IU/kg IV (same as adult)
Route Intravenous (IV) — slow infusion
Onset Symptom improvement within 30–60 minutes
PBS status Authority Required — Specialist · Available via Special Access Scheme (SAS Category B) through hospital pharmacies
💉
Icatibant
Firazyr® · 30 mg/3 mL pre-filled syringe · Bradykinin B₂-receptor antagonist
Adult dose 30 mg SC into abdominal wall; may repeat every 6 hours (max 3 doses/24 h)
Paediatric dose Not established for < 18 years in Australia; specialist use only
Route Subcutaneous (SC) — self-administration training available
PBS status Authority Required — Specialist · SAS Category B
💊
Tranexamic Acid
Cyklokapron® · Antifibrinolytic
Adult dose 1 g IV over 10 minutes; may be repeated after 1 hour if no response
Paediatric dose 20 mg/kg IV (max 1 g)
Role Second-line for HAE if C1-INH concentrate or icatibant unavailable; also used for long-term prophylaxis (1 g PO TDS)
PBS status ✔ PBS General Benefit

ACE-Inhibitor Angioedema — Management

⚠️
Permanently discontinue the ACE inhibitor. Do not rechallenge. Document clearly in the medical record and Allergies/Adverse Drug Reactions as a life-threatening reaction. Inform the patient, GP, pharmacist, and all treating specialists. Consider alerting via My Health Record adverse-reaction listing.

If the attack is bradykinin-mediated and targeted HAE therapies are available, consider icatibant or C1-INH concentrate under specialist guidance. Evidence is emerging but not yet definitive. Icatibant has shown benefit in small RCTs for ACE-inhibitor angioedema.

For ACE-inhibitor angioedema with airway compromise that is not responding to standard measures, discuss with the on-call immunologist or contact the Australian HAE Helpline (through HAE Australasia) for advice on emergency access to C1-INH concentrate.

Observation & Disposition

Mild
Isolated Facial / Extremity Swelling
No airway involvement, no dysphagia, no respiratory distress, responds to initial therapy within 2 hours.
Setting: ED observation 4–6 hours post-treatment; discharge with action plan, oral antihistamine, GP follow-up in 48 hours
Moderate
Tongue / Soft Palate Swelling Without Stridor
Mild dysphagia, globus sensation, visible uvula or tongue oedema but no airway compromise. Slow progression or incomplete response to initial therapy.
Setting: Hospital admission; continuous monitoring; ENT / anaesthetic review; repeat targeted therapy if bradykinin-mediated; observe minimum 24 hours
Severe
Airway Compromise / Laryngeal Angioedema
Stridor, severe dyspnoia, inability to handle secretions, rapidly progressive swelling, hoarseness / aphonia.
Setting: ICU / HDU; immediate senior anaesthetic involvement; prepare for intubation or surgical airway; IV adrenaline infusion if allergic; C1-INH or icatibant if HAE

Long-Term Prophylaxis for HAE

Long-term prophylaxis (LTP) is indicated for patients with ≥ 1 attack per month, significant disease burden, laryngeal attack history, or limited access to on-demand therapy. Options available in Australia:

💊
Danazol
Danocrine® · Attenuated androgen
Adult dose 200 mg PO daily; titrate to lowest effective dose (may reduce to 100 mg on alternate days)
Monitoring LFTs every 6 months; lipid profile; CBC; liver ultrasound annually
PBS status PBS Restricted Benefit
💊
Tranexamic Acid
Cyklokapron® · Antifibrinolytic — prophylactic dosing
Adult dose 1 g PO TDS (3 g/day total)
Paediatric dose 25 mg/kg PO TDS (max 1 g TDS)
Renal adjustment Reduce dose if eGFR < 30 mL/min
PBS status ✔ PBS General Benefit
💉
Subcutaneous C1-Inhibitor (Concentrated)
Haegarda® · Plasma-derived · SC prophylaxis
Adult dose 60 IU/kg SC twice weekly
Advantage Self-administered at home; steadier C1-INH levels than IV dosing
PBS status Authority Required — Specialist · SAS / compassionate access

Special Populations

🤰
Pregnancy & Breastfeeding
HAE in pregnancy: Attack frequency may increase in the second and third trimesters. C1-INH concentrate is the preferred on-demand therapy (Category B2). Tranexamic acid may be continued but assess risk–benefit. Danazol is contraindicated (teratogenic — virilisation of female foetus).
Allergic angioedema: Adrenaline remains first-line in pregnancy — risk of untreated anaphylaxis outweighs theoretical fetal risk. Use lowest effective dose.
👶
Paediatric Considerations
HAE onset: Mean age of first attack is 8–12 years but may present as early as age 2. Recurrent abdominal pain in a child with family history of HAE warrants C4 screening.
Adrenaline autoinjectors: EpiPen® Jr (0.15 mg) for 15–30 kg; EpiPen® (0.3 mg) for > 30 kg. Train families in use.
Weight-based dosing for all emergency medications is critical — refer to APLS or local paediatric guidelines.
👴
Elderly Patients
Higher prevalence of ACE-inhibitor use — maintain a high index of suspicion for drug-induced angioedema, even if the medication has been taken for years without issue.
Corticosteroid side-effects (hyperglycaemia, delirium) require monitoring during prolonged treatment courses.
🫘
Renal Impairment
Tranexamic acid: Dose reduction required if eGFR < 30 mL/min — risk of accumulation and seizures.
C1-INH concentrate: No renal adjustment required; safe in dialysis patients.
🫁
Hepatic Impairment
Danazol: Contraindicated in significant hepatic disease; monitor LFTs closely in all patients.
C1-INH concentrate is safe — no hepatic dose adjustment.
🛡️
Immunocompromised Patients
Acquired C1-INH deficiency should be considered in patients with lymphoproliferative disorders presenting with new-onset angioedema.
Exclude infection-related triggers (e.g., hepatitis B/C associated cryoglobulinaemia).

Aboriginal and Torres Strait Islander Health Considerations

Aboriginal and Torres Strait Islander Health
Epidemiology & burden
Australian Institute of Health and Welfare (AIHW) data indicate that Aboriginal and Torres Strait Islander peoples experience higher rates of allergic disease and hospitalisation for anaphylaxis/angioedema compared with non-Indigenous Australians, though specific angioedema data remain limited. Medication-related angioedema is particularly relevant given high rates of cardiovascular disease and ACE-inhibitor prescribing in Indigenous health services.
Remote & rural access
Many communities are hours from the nearest hospital with anaesthetic or ENT capability. Laryngeal angioedema in a remote clinic setting is a critical emergency — the Royal Flying Doctor Service (RFDS) must be contacted immediately. Ensure community health centres stock adrenaline ampoules and are trained in IM injection technique. Telehealth consultation with a clinical immunologist (via the Australian Telehealth Network) can facilitate acute decision-making.
Medication access
Adrenaline autoinjectors (EpiPen® / Anapen®) are available under PBS for patients with a history of anaphylaxis, but cost and remoteness remain barriers. Advocate for patients to receive autoinjectors through Closing the Gap PBS co-payment provisions (no patient co-payment for eligible Indigenous patients). C1-INH concentrate access requires metropolitan hospital pharmacy — arrange RFDS transfer protocols for confirmed HAE patients in remote areas.
Diagnostic delay
HAE may be underdiagnosed in Indigenous Australians due to limited access to specialist immunology services and complement testing. Consider screening C4 level in any Indigenous patient with recurrent unexplained swelling, particularly with family history. Remote pathology services can perform C4 testing — arrange through local Aboriginal Health Worker or Remote Area Nurse.
Cultural safety
Engage Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers in patient education and care planning. Provide culturally appropriate written materials in plain English and, where possible, in relevant First Nations languages. Use the National Aboriginal Community Controlled Health Organisation (NACCHO) frameworks for chronic disease management. Respect kinship structures in family education about hereditary conditions — consider involving Elders where appropriate and with patient consent.
Action plans
Ensure all patients receive a written angioedema/anaphylaxis action plan adapted for the remote setting. Include clear instructions for community health workers on when to call RFDS. Register confirmed HAE patients with HAE Australasia for ongoing support and access to emerging therapies.

📚 References

  1. 1. Maurer M, Magerl M, Ansotegui I, et al. The international WAO/EAACI guideline for the management of hereditary angioedema — the 2021 revision and update. World Allergy Organ J. 2022;15(1):100627.
  2. 2. Betschel S, Badiou J, Binkley K, et al. The International/Canadian Hereditary Angioedema Guideline. Allergy Asthma Clin Immunol. 2019;15:72.
  3. 3. Australasian Society of Clinical Immunology and Allergy (ASCIA). ASCIA guidelines for prevention of anaphylaxis in schools, preschools and childcare. Sydney: ASCIA; 2023.
  4. 4. Cicardi M, Aberer W, Banerji A, et al. Classification, diagnosis, and approach to treatment for angioedema: consensus report from the Hereditary Angioedema International Working Group. Allergy. 2014;69(5):602–616.
  5. 5. Bernstein JA, Cremonesi A, Hoffmann TK, Hollingsworth J. Angioedema in the emergency department: a practical guide to differential diagnosis and management. Int J Emerg Med. 2017;10(1):15.
  6. 6. Banerji A, Clark S, Bland K, et al. ACE-inhibitor angioedema in the emergency department: clinical characteristics, management, and outcomes. J Allergy Clin Immunol Pract. 2020;8(10):3385–3392.
  7. 7. Pharmaceutical Benefits Scheme (PBS). Australian Government Department of Health. Available at: https://www.pbs.gov.au. Accessed June 2025.
  8. 8. Australian Commission on Safety and Quality in Health Care (ACSQHC). National Safety and Quality Health Service Standards. 2nd ed. Sydney: ACSQHC; 2021.
  9. 9. Australian Institute of Health and Welfare (AIHW). Allergic disease in Australia. Cat. no. ACM 35. Canberra: AIHW; 2023.
  10. 10. HAE Australasia. Living with hereditary angioedema in Australia and New Zealand. Patient registry report. Sydney: HAE Australasia; 2023.
  11. 11. Frank MM, Gelfand JA, Atkinson JP. Hereditary angioedema: the clinical syndrome and its management. Ann Intern Med. 1976;84(5):580–593.
  12. 12. RHDAustralia (Northern Territory Department of Health and Menzies School of Health Research). The Australian guidelines for prevention, diagnosis and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: RHDAustralia; 2020. [Referenced for ATSI health frameworks applicable across clinical guidelines.]
  13. 13. Sinert R, Levy P, Bernstein JA, et al. Randomized trial of icatibant for ACE-inhibitor-induced angioedema in the emergency department. Ann Emerg Med. 2017;69(4):389–397.
  14. 14. Lumry WR, Li HH, Levy RJ, et al. Randomized placebo-controlled trial of the bradykinin B₂ receptor antagonist icatibant for the treatment of acute attacks of hereditary angioedema: the FAST-3 trial. Ann Allergy Asthma Immunol. 2011;107(6):529–537.
  15. 15. The Australasian Society of Clinical Immunology and Allergy (ASCIA). Position statement — prevention of anaphylaxis. Sydney: ASCIA; 2024.
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).
for PBS-listed medicines at participating pharmacies.
Cultural safety
Engagement with Aboriginal Community Controlled Health Organisations (ACCHOs) is essential. Cultural safety training for non-Indigenous clinicians, use of Aboriginal Health Workers and Liaison Officers, and incorporation of traditional healing practices alongside Western medicine improve treatment adherence and outcomes. Avoidance of eye contact, respect for gender-sensitive examination practices, and understanding of sorry business protocols are critical elements of culturally safe care.
Medication adherence
Complex DMARD regimens with frequent monitoring requirements present adherence challenges. Long-acting depot injections (e.g., methotrexate SC) may improve adherence compared to oral regimens. Community pharmacy partnerships through the Indigenous Pharmacy Programmes improve medication management.
Specific conditions
Rheumatic heart disease (RHD) requires secondary prophylaxis with benzathine penicillin G (BPG) 1.2 MU IM every 3–4 weeks for a minimum of 10 years or until age 21 (whichever is longer). RHD registers (e.g., NT RHD Register) facilitate recall and follow-up. The Australian RHD Endgame Strategy targets elimination by 2031.
Referral pathways
Referral through ACCHOs and Aboriginal Hospital Liaison Officers (AHLOs) improves engagement. The Specialist Outreach Assistance Programme provides funded specialist visits to remote communities. NT, WA, and QLD have specific rheumatology outreach programmes targeting Indigenous communities.

📚 References

  1. 1. Australian Institute of Health and Welfare (AIHW). Autoimmune disease in Australia. Cat. no. PHE 312. Canberra: AIHW; 2023.
  2. 2. Fraenkel L, Bathon JM, England BR, et al. 2021 American College of Rheumatology guideline for the treatment of rheumatoid arthritis. Arthritis Care Res. 2021;73(7):924–939.
  3. 3. Fanouriakis A, Kostopoulou M, Alber K, et al. 2019 update of the EULAR recommendations for the management of systemic lupus erythematosus. Ann Rheum Dis. 2019;78(6):736–745.
  4. 4. Chung SA, Langford CA, Maz M, et al. 2021 American College of Rheumatology/Vasculitis Foundation guideline for the management of antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Care Res. 2021;73(11):1583–1599.
  5. 5. Smolen JS, Landewé RBM, Bijlsma JWJ, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2022 update. Ann Rheum Dis. 2023;82(1):3–18.
  6. 6. Australian Technical Advisory Group on Immunisation (ATAGI). Australian Immunisation Handbook. Australian Government Department of Health; 2024. Available from: immunisationhandbook.health.gov.au.
  7. 7. Rheumatic Heart Disease Australia (RHDAustralia). The 2020 Australian guideline for prevention, diagnosis, and management of acute rheumatic fever and rheumatic heart disease. 3rd ed. Darwin: Menzies School of Health Research; 2020.
  8. 8. Pharmaceutical Benefits Scheme (PBS). PBS Schedule. Australian Government Department of Health. Available from: pbs.gov.au. Accessed 2024.
  9. 9. Agarwal S, Cunnington J, Nossent J. Autoimmune disease in Indigenous Australians: a systematic review. Int J Rheum Dis. 2021;24(12):1487–1498.
  10. 10. Pisetsky DS. Antinuclear antibody testing — misunderstood or misused? Clin Immunol. 2023;255:109717.
  11. 11. Bertsias GK, Tektonidou M, Amoura Z, et al. Joint European League Against Rheumatism and European Renal Association–European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis. 2012;71(11):1771–1782.
  12. 12. Ledingham J, Deighton C; British Society for Rheumatology Standards, Audit and Guidelines Working Group. Update on the British Society for Rheumatology guidelines for prescribing TNFα blockers in adults with rheumatoid arthritis. Rheumatology. 2005;44(2):155–158.
  13. 13. National Health and Medical Research Council (NHMRC). National statement on ethical conduct in human research. Canberra: NHMRC; 2023 (updated).